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Drug Design, Development and Therapy Volume 9, 2015 - Issue
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Original Research

Synthesis and characterization of tumor-targeted copolymer nanocarrier modified by transferrin

Ran Liu1 Department of Hematology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China;2 Faculty of Oncology, Medical School, Southeast University, Nanjing, People’s Republic of China
,
Yonglu Wang1 Department of Hematology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China;3 College of Pharmacy, Nanjing University of Technology, Nanjing, People’s Republic of China
,
Xueming Li3 College of Pharmacy, Nanjing University of Technology, Nanjing, People’s Republic of China
,
Wen Bao1 Department of Hematology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China;2 Faculty of Oncology, Medical School, Southeast University, Nanjing, People’s Republic of China
,
Guohua Xia1 Department of Hematology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China;2 Faculty of Oncology, Medical School, Southeast University, Nanjing, People’s Republic of China
,
Wei Chen3 College of Pharmacy, Nanjing University of Technology, Nanjing, People’s Republic of China
,
Jian Cheng1 Department of Hematology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China;2 Faculty of Oncology, Medical School, Southeast University, Nanjing, People’s Republic of China
,
Yuanlong Xu3 College of Pharmacy, Nanjing University of Technology, Nanjing, People’s Republic of China
,
Liting Guo1 Department of Hematology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China;2 Faculty of Oncology, Medical School, Southeast University, Nanjing, People’s Republic of China
&
Baoan Chen1 Department of Hematology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China;2 Faculty of Oncology, Medical School, Southeast University, Nanjing, People’s Republic of ChinaCorrespondence[email protected]
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Pages 2705-2719 | Published online: 22 May 2015

Figures & data

Figure 1 Reaction diagram of crosslink Tf.

Abbreviations: PLGA, poly(lactic-co-glycolic acid); PLL, poly-L-lysine; PEG, polyethylene glycol; PBS, phosphate buffered saline; Tf, transferrin.
Figure 1 Reaction diagram of crosslink Tf.

Figure 2 Structural model of Tf-modified copolymer drug-loaded NPs.

Abbreviations: PLGA, poly(lactic-co-glycolic acid); PLL, poly-L-lysine; PEG, polyethylene glycol; Tf, transferrin; NPs, nanoparticles.
Figure 2 Structural model of Tf-modified copolymer drug-loaded NPs.

Figure 3 1H NMR spectrum.

Notes: (A) PLL–Cbz; (B) PLGA–PLL–Cbz; (C) PLGA–PLL (deprotected); (D) CDI–PEG–CDI; and (E) PLGA–PLL–PEG–CDI.
Abbreviations: 1H NMR, proton nuclear magnetic resonance; PLL, poly-L-lysine; Cbz, carbobenzoxy; PLGA, poly(lactic-co-glycolic acid); CDI, N,N-carbony ldiimidazole; PEG, polyethylene glycol.
Figure 3 1H NMR spectrum.

Figure 4 Effect of formulation parameters on the particle size and drug loadings of DNR and Tet in DNR/Tet–PLGA–PLL–PEG–Tf-NPs.

Notes: (A) Mw of PLGA; (B) concentration of PLGA–PLL–PEG–Tf; (C) volume ratio of A/D; (D) concentration of PVA in the external aqueous phase; (E) volume ratio of I/E; and (F) surfactant type of the internal aqueous phase.
Abbreviations: DNR, daunorubicin; Tet, tetrandrine; PVA, polyvinyl alcohol; PLGA, poly(lactic-co-glycolic acid); PLL, poly-L-lysine; PEG, polyethylene glycol; Tf, transferrin; NPs, nanoparticles; Mw, molecular weight; A/D, acetone and dichloromethane; I/E, the internal aqueous phase to the external aqueous phase.
Figure 4 Effect of formulation parameters on the particle size and drug loadings of DNR and Tet in DNR/Tet–PLGA–PLL–PEG–Tf-NPs.

Figure 5 Effects of cryoprotectants on the mean diameter after freeze-drying.

Figure 5 Effects of cryoprotectants on the mean diameter after freeze-drying.

Figure 6 Gel permeation chromatography.

Notes: (A) Elution time of Tf; and (B) elution time of DNR/Tet–PLGA–PLL–PEG–Tf-NPs.
Abbreviations: min, minutes; Tf, transferrin; DNR, daunorubicin; Tet, tetrandrine; PLGA, poly(lactic-co-glycolic acid); PLL, poly-L-lysine; PEG, polyethylene glycol; NPs, nanoparticles.
Figure 6 Gel permeation chromatography.

Figure 7 Solution color of DNR/Tet–PLGA–PLL–PEG–Tf-NPs (purple liquid) and DNR/Tet–PLGA–PLL–PEG-NPs (green liquid).

Abbreviations: DNR, daunorubicin; Tet, tetrandrine; PLGA, poly(lactic-co-glycolic acid); PLL, poly-L-lysine; PEG, polyethylene glycol; Tf, transferrin; NPs, nanoparticles.
Figure 7 Solution color of DNR/Tet–PLGA–PLL–PEG–Tf-NPs (purple liquid) and DNR/Tet–PLGA–PLL–PEG-NPs (green liquid).

Figure 8 DNR/Tet–PLGA–PLL–PEG–Tf-NPs under TEM and histogram of particle size distribution.

Notes: (A) DNR/Tet–PLGA–PLL–PEG–Tf-NPs under TEM (scale bar: 0.5 μm); and (B) histogram of particle size distribution.
Abbreviations: DNR, daunorubicin; Tet, tetrandrine; PLGA, poly(lactic-co-glycolic acid); PLL, poly-L-lysine; PEG, polyethylene glycol; Tf, transferrin; NPs, nanoparticles; TEM, transmission electron microscopy.
Figure 8 DNR/Tet–PLGA–PLL–PEG–Tf-NPs under TEM and histogram of particle size distribution.

Figure 9 Particle size distribution of DNR/Tet–PLGA–PLL–PEG–Tf-NPs.

Abbreviations: DNR, daunorubicin; Tet, tetrandrine; PLGA, poly(lactic-co-glycolic acid); PLL, poly-L-lysine; PEG, polyethylene glycol; Tf, transferrin; NPs, nanoparticles.
Figure 9 Particle size distribution of DNR/Tet–PLGA–PLL–PEG–Tf-NPs.

Figure 10 DSC thermography.

Notes: Green line: Tet; blue line: DNR; red line: PLGA–PLL–PEG-NPs; yellow line: DNR/Tet–PLGA–PLL–PEG–Tf-NPs; and purple line: mixture of DNR and Tet samples.
Abbreviations: DSC, differential scanning capacity thermography; exo, exothermic; Tet, tetrandrine; DNR, daunorubicin; PLGA, poly(lactic-co-glycolic acid); PLL, poly-L-lysine; PEG, polyethylene glycol; NPs, nanoparticles; Tf, transferrin.
Figure 10 DSC thermography.

Figure 11 Release profiles of DNR and Tet from DNR/Tet–PLGA–PLL–PEG–Tf-NPs.

Abbreviations: DNR, daunorubicin; Tet, tetrandrine; PLGA, poly(lactic-co-glycolic acid); PLL, poly-L-lysine; PEG, polyethylene glycol; Tf, transferrin; NP, nanoparticles; h, hours.
Figure 11 Release profiles of DNR and Tet from DNR/Tet–PLGA–PLL–PEG–Tf-NPs.

Figure 12 Cytotoxic effect of PLGA–PLL–PEG–Tf-NPs on K562/ADR cells for different times.

Abbreviations: h, hours; PLGA, poly(lactic-co-glycolic acid); PLL, poly-L-lysine; PEG, polyethylene glycol; Tf, transferrin; NPs, nanoparticles.
Figure 12 Cytotoxic effect of PLGA–PLL–PEG–Tf-NPs on K562/ADR cells for different times.

Figure 13 Cell viability of K562/ADR cells.

Notes: (A) Cells treated with different concentrations of Tet for various times; and (B) Cells treated with different concentrations of DNR, DNR&Tet, DNR/Tet–PLGA–PLL–PEG-NPs, or DNR/Tet–PLGA–PLL–PEG–Tf-NPs for 48 h.
Abbreviations: DNR, daunorubicin; Tet, tetrandrine; PLGA, poly(lactic-co-glycolic acid); PLL, poly-L-lysine; PEG, polyethylene glycol; Tf, transferrin; NPs, nanoparticles; DNR&Tet, daunorubicin and tetrandrine; h, hours.
Figure 13 Cell viability of K562/ADR cells.

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